The present application relates to methods of treating or preventing proliferative disease, particularly cancer, by administering to a subject a composition comprising lycopene and alpha-tocopherol.
Lycopene, a natural red carotenoid found in nature in high amounts in tomatoes and also in tomato-derived products, is a potent antioxidant and free radical quencher. Lycopene has been found concentrated in various body tissues, such as liver, adrenal, and adipose tissues, as well as in the prostate. In vitro studies have shown that lycopene has a growth inhibitory effect on mammary, lung, and endometrial carcinoma cell proliferation at and an inhibitory effect on prostate carcinoma cell proliferation at concentrations of 50 xcexcM and above. Little physiological significance can be attributed to the latter finding as the inhibitory concentrations in vitro far exceeded typical physiological plasma concentrations for lycopene. Epidemiological studies have associated lycopene intake with a decreased risk of prostate cancer.
Tocopherol compounds, also called vitamin E, are active components in vegetable oils. Vitamin E activity refers to the physiological activity of this group of nutrient materials. Materials having a vitamin E activity all belong to a distinct series of compounds which are all derivatives of chroman-6-ol. These compounds are all tocol derivatives having an isoprenoid C16-sidechain. The term xe2x80x9ctocolxe2x80x9d is used to mean 2-methyl-2-(4xe2x80x2,8xe2x80x2,12xe2x80x2-trimethyltridecyl) chroman-6-ol. These compounds are alpha-, beta-, gamma-, and delta-tocopherol, and are of primary importance for vitamin E activity.
Alpha-tocopherol is produced commercially for use as a feed supplement for domestic animals as a source of Vitamin E activity and as a nutrient supplement for humans. Tocopherols are also used in food technology as an antioxidant to retard the development of rancidity in fatty materials. The tocopherols are found widely distributed in normal foods, occurring in the highest concentration in the cereal grain oils, principally in corn and wheat oils, but also in barley and rye oils. They are also found in other vegetable oils such as safflower, soybean, peanut, cottonseed, linseed, sunflower, rapeseed and palm, and in other vegetable sources, e.g., palm leaves, lettuce, alfalfa, rubber latex and a variety of other plant materials. The proportion of the most active form, the D-alpha-tocopherol, varies widely among the different sources. Two sources having the highest levels of D-alpha-tocopherol are safflower oil and sunflower oil, although the most commonly available source is soybean oil, which has a considerably lower percent of D-alpha-tocopherol than safflower and sunflower oils, and with significantly higher percentages of the gamma- and delta-homologues. In addition to being a source for tocopherol homologues, palm oil, oats, rye, and barley also contain tocotrienol.
Of the tocopherols, alpha-tocopherol has the highest vitamin E activity and is the most valuable. Biochemical studies have shown that alpha-tocopherol inhibits cell proliferation in certain sensitive cell lines. Epidemiological studies also have associated alpha-tocopherol intake with a decreased risk of prostate cancer.
The present invention is based upon the discovery that lycopene and alpha-tocopherol synergize to inhibit cancer cell proliferation, that is, the combination of lycopene and alpha-tocopherol inhibits cancer cell proliferation to a greater extent than the additive inhibitory effects of lycopene and alpha-tocopherol alone on cancer cell proliferation.
Accordingly, the present invention provides methods of treating or preventing proliferative disease, particularly cancer, in a subject in need thereof, preferably a human subject, by administration of a composition comprising both lycopene and alpha-tocopherol. The composition containing lycopene and alpha-tocopherol is preferably administered so as to result in plasma levels of 0.01 to 5.0 xcexcM lycopene and 1 to 100 4xcexcM alpha-tocopherol.